The studies proposed in this project continue to follow the major aspects of the original research plan: 1. Study the pharmacologic actions as well as some of the biochemical and biophysical mechanisms of action of neurohypophyseal polypeptide hormones (e.g. vasopressin, oxytocin) catecholamines, ergot alkaloid peptides and prostaglandins on micro- and macro-vascular smooth muscle. 2. Search for analogues and/or homologues of the neurohypophyseal hormones, catecholamines, ergot alkaloids and prostaglandins which exert selective vasotropic effects on specific types of muscular microvessels in the microcirculation. 3. Having documented the foregoing as a frame of reference some of these molecules will be examined for their pharmacodynamic actions and structure-activity relationships on micro-and macro-vascular muscle both in vivo and in vitro in different vascular beds of different laboratory species of animals as well as human blood vessels. 4. As the peripheral site(s) of action of the synthetic molecules are determined in the various regional microcirculatory beds, some will be selected for trial as therapeutic agents in the treatment of different types of circulatory shock; the latter to serve as a potential source of new drugs for clinical application. 5. Explore sex hormones and other modifiers of vascular reactivity in relation to circulatory shock and the selective actions of neurohypophyseal peptide and catecholamine molecules. 6. Develop methods for assessing at a tissue-level the stage(s) of the shock syndrome and its response to thrapeutic modalities.